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Assessing coronary microvascular dysfunction in refractory no-reflow: Insights from dynamic myocardial perfusion scintigraphy and cardiac MRI 评估难治性非再流患者冠状动脉微血管功能障碍:来自动态心肌灌注显像和心脏MRI的见解
IF 2.7 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE Pub Date : 2025-08-20 DOI: 10.1016/j.mvr.2025.104862
Stanislav Dil, Vyacheslav Ryabov, Leonid Maslov, Olga Mochula, Andrey Mochula, Maria Kercheva, Konstantin Zavadovsky, Evgeny Vyshlov

Background

Refractory no-reflow correlates with worse outcomes, including larger infarct sizes, impaired ventricular function, and higher mortality rates, despite advances in percutaneous coronary intervention (PCI). Microvascular obstruction (MVO) and increased left ventricular end-diastolic pressure (LVEDP) are implicated in the pathogenesis, potentially exacerbating ischemic injury and limiting myocardial recovery. While pressure-wire–derived indices such as the Index of Microcirculatory Resistance (IMR) have been validated against MRI-defined MVO in STEMI populations, their invasive nature and procedural complexity limit broad adoption. In contrast, combining dynamic SPECT and cardiac MRI enables a comprehensive non-invasive functional-structural evaluation of coronary microvascular function in refractory no-reflow.

Methods

This study is a post hoc analysis of a larger randomized controlled trial (RCT) evaluating the efficacy and safety of intracoronary epinephrine in patients with refractory no-reflow post-PCI (ClinicalTrials.gov NCT04573751). We evaluated global coronary flow metrics (RMBF, SMBF, gRFI) derived from SPECT and assessed structural markers of microvascular injury (infarct size, MVO) on MRI. Echocardiographic estimations of LVEDP were also analyzed.

Results

Dynamic SPECT revealed suboptimal stress myocardial blood flow in most patients, highlighting microvascular impairment. Elevated estimated LVEDP was significantly correlated with indexed MVO (rs = 0.678, p = 0.001). Traditional flow reserve metrics showed limited sensitivity, whereas global relative flow increase (gRFI) showed a statistically significant correlation with MVO, highlighting its added value in detecting stress-induced perfusion abnormalities. Given the small sample and potential outlier influence, this observation should be considered hypothesis-generating.

Conclusion

Our findings support that functional impairments—particularly elevated LVEDP and reduced gRFI—are associated with refractory no-reflow. In particular, gRFI may serve as a promising non-invasive marker of microvascular dysfunction, complementing structural imaging. None-theless, further validation in larger cohorts is needed. This study advocates for refined multimodal imaging strategies and tailored therapeutic approaches targeting dynamic microvascular disturbances to improve outcomes in refractory no-reflow.
背景:尽管经皮冠状动脉介入治疗(PCI)技术有所进步,但难治性非再流与更糟糕的结果相关,包括更大的梗死面积、心室功能受损和更高的死亡率。微血管阻塞(MVO)和左室舒张末期压(LVEDP)升高与发病机制有关,可能加剧缺血性损伤并限制心肌恢复。虽然压力线衍生的指标,如微循环阻力指数(IMR)已经在STEMI人群中针对mri定义的MVO进行了验证,但其侵入性和程序复杂性限制了其广泛采用。相比之下,结合动态SPECT和心脏MRI可以对难治性无血流障碍患者的冠状动脉微血管功能进行全面的无创功能结构评估。方法:本研究是一项大型随机对照试验(RCT)的事后分析,该试验评估了冠状动脉内肾上腺素治疗难治性pci后无再流患者的有效性和安全性(ClinicalTrials.gov NCT04573751)。我们评估了SPECT得出的全球冠状动脉血流指标(RMBF, SMBF, gRFI),并评估了MRI上微血管损伤的结构标记(梗死面积,MVO)。超声心动图估计LVEDP也进行了分析。结果动态SPECT显示大多数患者的应激心肌血流量不理想,微血管损伤突出。估计LVEDP升高与MVO指数显著相关(rs = 0.678, p = 0.001)。传统的流量储备指标灵敏度有限,而全局相对流量增加(gRFI)与MVO的相关性具有统计学意义,突出了其在检测应力诱导的灌注异常方面的附加价值。考虑到样本小和潜在的异常值影响,这一观察结果应该被认为是假设生成。结论:我们的研究结果支持功能损伤——特别是LVEDP升高和grfi降低——与难治性无血流相关。特别是,gRFI可以作为微血管功能障碍的一种有前途的非侵入性标志物,补充结构成像。然而,需要在更大的队列中进一步验证。本研究提倡完善的多模式成像策略和针对动态微血管紊乱的量身定制的治疗方法,以改善难治性无再流的预后。
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引用次数: 0
Retinal blood flow in eyes with primary open-angle glaucoma using a new Adaptive Optics Laser Doppler Velocimeter device 新型自适应光学激光多普勒测速仪在原发性开角型青光眼视网膜血流中的应用。
IF 2.7 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE Pub Date : 2025-08-16 DOI: 10.1016/j.mvr.2025.104858
Ohud Altuwaym , Martial Geiser , Thibaud Mautuit , Frédéric Truffer , Christophe Chiquet

Purpose

To measure retinal blood flow (RBF) in the retinal veins of patients with primary open-angle glaucoma (POAG) and to compare it with healthy controls. A secondary objective was to determine any correlation between RBF and visual field (VF) loss or retinal nerve-fiber layer (RNFL) thickness.

Method

Twelve patients with POAG and 11 healthy controls were included in a prospective single-center study. Our prototype Adaptive Optics Laser Doppler Velocimeter (AO-LDV) consisted of a laser Doppler velocimeter combined with an adaptive optic fundus camera (rtx1, Imagine Eyes®) allowing measurement of blood vessel diameter and therefore, calculation of blood flow within the vessel. Blood flow in the superior temporal vein (STV) was compared with that in the inferior temporal vein (ITV). All subjects underwent eye examinations including visual field (Humphrey 24-2 SITA-standard strategy) and measurement of retinal nerve-fiber layer (RNFL) thickness using a Cirrus HD-OCT (optic disc 200 × 200 cube) protocol. Sectoral structure-function relationships were studied in the glaucoma group.

Results

The velocity in the STV was lower in the glaucoma group (6.30 ± 1.6 mm/s) compared to the control group (8.6 ± 2.8 mm/s, p = 0.07), with no significant differences in the ITV. There were no significant differences in STV or ITV diameters between the groups. We found no relationship between either STV or ITV retinal blood flow and visual field or RNFL thickness.

Conclusion

Our prototype AO-LDV allowed accurate measurement of RBF in patients with glaucoma and showed that RBF was not reduced in the early or moderate stages of glaucoma. These preliminary results should be confirmed in a larger study, especially in late-stage glaucoma.
目的:测定原发性开角型青光眼(POAG)患者视网膜静脉血流(RBF),并与健康对照进行比较。次要目的是确定RBF与视野(VF)损失或视网膜神经纤维层(RNFL)厚度之间的相关性。方法:采用前瞻性单中心研究,选取12例POAG患者和11例健康对照。我们的原型自适应光学激光多普勒测速仪(AO-LDV)由激光多普勒测速仪和自适应光学眼底相机(rtx1, Imagine Eyes®)组成,可以测量血管直径,从而计算血管内的血流。比较颞上静脉(STV)与颞下静脉(ITV)的血流情况。所有受试者均接受眼部检查,包括视野(Humphrey 24-2 sita标准策略)和使用Cirrus HD-OCT(视盘200 × 200立方)测量视网膜神经纤维层(RNFL)厚度。青光眼组研究部门结构-功能关系。结果:青光眼组STV速度(6.30 ± 1.6 mm/s)低于对照组(8.6 ± 2.8 mm/s, p = 0.07),ITV无显著性差异。两组间STV或ITV直径无显著差异。我们发现STV或ITV视网膜血流与视野或RNFL厚度没有关系。结论:我们的原型AO-LDV可以准确测量青光眼患者的RBF,并显示在青光眼的早期或中度阶段RBF不会降低。这些数据表明,在青光眼的早期阶段,视网膜血流量并没有明显减少。这些初步结果应在更大的研究中得到证实,特别是在晚期青光眼中。
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引用次数: 0
Intermittent heat stress facilitates the autophagy and apoptosis of the vascular endothelium in spontaneously hypertensive rats via the AMPK/mTOR/ULK1 pathway 间歇性热应激通过AMPK/mTOR/ULK1通路促进自发性高血压大鼠血管内皮的自噬和凋亡
IF 2.7 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE Pub Date : 2025-08-08 DOI: 10.1016/j.mvr.2025.104857
Chunli Yang , Huijuan Zhao , Xiaomin Wu , Wei Tuo , Ling Hou , Dahai Chai , Guanghua Li
This study examined the autophagy and apoptosis of vascular endothelial cells in spontaneously hypertensive rats (SHRs) under intermittent heat stress and determined whether the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51 like autophagy activating kinase (ULK1) pathway is involved in autophagy regulation. Wistar-Kyoto (WKY) rats were assigned to control (WKY-CN), intermittent heat stress (WKY-8), and continuous heat stress (WKY-24) groups. SHRs were also assigned to three groups: SHR-CN, SHR-8, and SHR-24. Western blotting assay, immunohistochemical assay, and immunofluorescence assay were performed for observing expression of proteins related to autophagy and apoptosis and the AMPK/mTOR/ULK1 pathway. Vascular endothelial cells underwent autophagy and apoptosis following heat stress, as revealed by high expression of autophagy- and apoptosis-related proteins. Heat stress elevated AMPK and ULK1 expression levels, whereas it decreased mTOR phosphorylation in SHR-8 and SHR-24 groups. Finally, the rats in SHR-8 group were administered an autophagy inducer (rapamycin, Rapa) and inhibitor (3-Methyladenine, 3-MA), respectively, for evaluating autophagy induction and inhibition. Following Rapa administration, LC3-II/LC3-I and Caspase-3 expression levels were elevated in the intermittent heat stress groups as compared to those in the control groups; in contrast, 3-MA attenuated cell death in the intermittent heat stress groups. Overall, this study demonstrated that intermittent heat stress elicits autophagy and apoptosis processes in vascular endothelial cells and that the AMPK/mTOR/ULK1 pathway participates in regulating autophagy and apoptosis.
本研究检测间歇性热应激下自发性高血压大鼠(SHRs)血管内皮细胞的自噬和凋亡情况,确定amp活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)/Unc-51样自噬激活激酶(ULK1)通路是否参与自噬调控。Wistar-Kyoto (WKY)大鼠分为对照组(WKY- cn)、间歇性热应激组(WKY-8)和持续性热应激组(WKY-24)。SHRs也被分为3组:shrr - cn、shrr -8和shrr -24。采用Western blot、免疫组化、免疫荧光法观察细胞自噬、凋亡相关蛋白及AMPK/mTOR/ULK1通路的表达情况。热应激后血管内皮细胞发生自噬和凋亡,自噬和凋亡相关蛋白高表达。热应激升高了SHR-8和SHR-24组AMPK和ULK1的表达水平,而降低了mTOR的磷酸化水平。最后,shr8组大鼠分别给予自噬诱导剂(雷帕霉素,Rapa)和抑制剂(3-甲基腺嘌呤,3-MA),评价自噬诱导和抑制作用。给药后,与对照组相比,间歇性热应激组LC3-II/LC3-I和Caspase-3表达水平升高;相反,3-MA可减轻间歇性热应激组的细胞死亡。综上所述,本研究表明间歇性热应激诱导血管内皮细胞自噬和凋亡过程,AMPK/mTOR/ULK1通路参与了自噬和凋亡的调控。
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引用次数: 0
Comparative analysis of superficial collecting lymph vessels in normal tissue and lymphedema using video-capillaroscopy 视频毛细血管镜下正常组织浅表集淋巴管与淋巴水肿的对比分析。
IF 2.7 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE Pub Date : 2025-08-05 DOI: 10.1016/j.mvr.2025.104842
Chihiro Matsui , Reiko Tsukuura , Toko Miyazaki , Shigeki Ishibashi , Takakuni Tanaka , Takayoshi Nishimura , Go Arai , Joseph M. Escandón , Hatan Mortada , Takumi Yamamoto

Introduction

Lymphedema is a chronic, progressive disorder characterized by impaired lymphatic transport, tissue swelling, and fibrosis. This study used video-capillaroscopy, a high-resolution imaging technique, to assess superficial collecting lymphatic vessels and their vasa vasorum in patients with lymphedema. By comparing these microvascular structures to those in healthy tissue, we aimed to identify early vascular changes contributing to disease progression.

Methods

VC recordings were retrospectively analyzed from 28 limbs in 17 patients with lower extremity lymphedema and 53 lymphatic vessels in 12 cancer patients undergoing reconstructive surgery. In the latter group, observations were performed on normal subcutaneous tissue exposed at the donor site during flap harvest. These areas showed no tumor involvement, regional metastasis, or prior chemotherapy/radiotherapy. Thus, all normal tissue observations were made on untreated, unaffected sites. VCLs were classified into six stages (0–5) based on morphology and flow. Vessel diameter and red blood cell (RBC) velocity were measured. Statistical significance was set at p < 0.05.

Results

In normal donor tissue, mean VCL main vessel diameter and RBC velocity were 0.038 ± 0.031 mm and 185 ± 160.5 μm/s. In lymphedema, these values were reduced to 0.033 ± 0.024 mm and 28.3 ± 36.8 μm/s (p < 0.001). VCL Stage 0 showed preserved flow (p = 0.178), while Stages 1–5 exhibited progressive impairment.

Conclusion

These findings suggest that early ischemic changes in the vasa vasorum may precede lymphatic dysfunction and fibrosis in lymphedema. Preserving microvascular integrity should be a therapeutic focus, alongside drainage support. Further studies are needed to clarify clinical relevance and optimize treatment strategies.
简介:淋巴水肿是一种慢性进行性疾病,以淋巴运输受损、组织肿胀和纤维化为特征。本研究使用视频毛细血管镜,一种高分辨率成像技术,来评估淋巴水肿患者的浅表收集淋巴管及其血管。通过将这些微血管结构与健康组织的微血管结构进行比较,我们旨在确定有助于疾病进展的早期血管变化。方法:回顾性分析17例下肢淋巴水肿患者28条肢体和12例肿瘤重建手术患者53条淋巴管的VC记录。在后一组中,观察在皮瓣收获期间暴露在供区正常皮下组织。这些区域未见肿瘤累及、局部转移或既往化疗/放疗。因此,所有正常组织的观察都是在未经治疗、未受影响的部位进行的。根据形态和流量将vcl分为6级(0-5级)。测量血管直径和红细胞流速。结果:在正常供体组织中,VCL主干血管直径和红细胞流速分别为0.038 ± 0.031 mm和185 ± 160.5 μm/s。在淋巴水肿中,这一数值分别降至0.033 ± 0.024 mm和28.3 ± 36.8 μm/s (p )。结论:这些结果提示,在淋巴水肿中,血管血管早期缺血改变可能早于淋巴功能障碍和纤维化。保持微血管的完整性应该是治疗的重点,同时支持引流。需要进一步的研究来阐明临床相关性和优化治疗策略。
{"title":"Comparative analysis of superficial collecting lymph vessels in normal tissue and lymphedema using video-capillaroscopy","authors":"Chihiro Matsui ,&nbsp;Reiko Tsukuura ,&nbsp;Toko Miyazaki ,&nbsp;Shigeki Ishibashi ,&nbsp;Takakuni Tanaka ,&nbsp;Takayoshi Nishimura ,&nbsp;Go Arai ,&nbsp;Joseph M. Escandón ,&nbsp;Hatan Mortada ,&nbsp;Takumi Yamamoto","doi":"10.1016/j.mvr.2025.104842","DOIUrl":"10.1016/j.mvr.2025.104842","url":null,"abstract":"<div><h3>Introduction</h3><div>Lymphedema is a chronic, progressive disorder characterized by impaired lymphatic transport, tissue swelling, and fibrosis. This study used video-capillaroscopy, a high-resolution imaging technique, to assess superficial collecting lymphatic vessels and their vasa vasorum in patients with lymphedema. By comparing these microvascular structures to those in healthy tissue, we aimed to identify early vascular changes contributing to disease progression.</div></div><div><h3>Methods</h3><div>VC recordings were retrospectively analyzed from 28 limbs in 17 patients with lower extremity lymphedema and 53 lymphatic vessels in 12 cancer patients undergoing reconstructive surgery. In the latter group, observations were performed on normal subcutaneous tissue exposed at the donor site during flap harvest. These areas showed no tumor involvement, regional metastasis, or prior chemotherapy/radiotherapy. Thus, all normal tissue observations were made on untreated, unaffected sites. VCLs were classified into six stages (0–5) based on morphology and flow. Vessel diameter and red blood cell (RBC) velocity were measured. Statistical significance was set at <em>p</em> &lt; 0.05.</div></div><div><h3>Results</h3><div>In normal donor tissue, mean VCL main vessel diameter and RBC velocity were 0.038 ± 0.031 mm and 185 ± 160.5 μm/s. In lymphedema, these values were reduced to 0.033 ± 0.024 mm and 28.3 ± 36.8 μm/s (<em>p</em> &lt; 0.001). VCL Stage 0 showed preserved flow (<em>p</em> = 0.178), while Stages 1–5 exhibited progressive impairment.</div></div><div><h3>Conclusion</h3><div>These findings suggest that early ischemic changes in the vasa vasorum may precede lymphatic dysfunction and fibrosis in lymphedema. Preserving microvascular integrity should be a therapeutic focus, alongside drainage support. Further studies are needed to clarify clinical relevance and optimize treatment strategies.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"162 ","pages":"Article 104842"},"PeriodicalIF":2.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Influence of pericyte-like vessel dilation on RBC flux in an In Vitro microvascular network 周细胞样血管扩张对体外微血管网络中红细胞通量的影响。
IF 2.7 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE Pub Date : 2025-08-05 DOI: 10.1016/j.mvr.2025.104846
Aurelia Bucciarelli, Dominik Obrist
Efficient oxygen delivery in the brain relies on a finely tuned balance between vascular architecture and dynamic flow regulation. While red blood cells (RBCs) passively flow through the capillary network, neurovascular coupling ensures that the blood supply adapts to meet the metabolic demands of active neurons. Pericytes, contractile cells embedded in the capillary walls, play a key role in this process by modulating capillary diameter in response to neural signals. While pericytes are believed to enable rapid and localized blood flow regulation, their contributions in time and space remain debated. This study investigates the effects of pericyte-like vessel dilation (i.e., pericyte relaxation) on RBC distribution and flow dynamics using an in vitro microfluidic model. We investigate how pericyte-induced dynamic cross-sectional changes affect RBC distribution and velocity in a capillary network. By employing a programmable pressure pump to simulate gradual variations in capillary diameter, we observed that short-time dilation increased RBC velocity and hematocrit near the dilation site, enhancing localized perfusion. In contrast, prolonged dilation led to a network-wide RBC redistribution minimizing hydraulic resistance, ultimately depleting hematocrit due to the network Fåhræus effect. These findings highlight the dynamic and adaptive nature of capillary blood flow, where sustained localized changes can propagate into systemic effects over time. More broadly, this study provides new insights into the interplay between localized flow regulation and systemic capillary network dynamics, revealing how geometric and dynamic factors govern RBC behavior and perfusion.
大脑中有效的氧气输送依赖于血管结构和动态血流调节之间的精细平衡。当红细胞被动地通过毛细血管网络流动时,神经血管耦合确保血液供应适应活跃神经元的代谢需求。周细胞,嵌入毛细血管壁的可收缩细胞,通过响应神经信号调节毛细血管直径,在这一过程中发挥关键作用。虽然周细胞被认为能够实现快速和局部的血流调节,但它们在时间和空间上的贡献仍然存在争议。本研究利用体外微流体模型研究周细胞样血管扩张(即周细胞松弛)对红细胞分布和血流动力学的影响。我们研究周细胞诱导的动态横截面变化如何影响毛细血管网络中的红细胞分布和速度。通过使用可编程压力泵模拟毛细血管直径的逐渐变化,我们观察到短时扩张增加了扩张部位附近的红细胞速度和红细胞压积,增强了局部灌注。相反,长时间的扩张导致整个网络范围内的红细胞再分布,使水力阻力最小化,最终由于网络f hræus效应而消耗红细胞压积。这些发现强调了毛细血管血流的动态和适应性,随着时间的推移,持续的局部变化可以传播成全身效应。更广泛地说,这项研究为局部血流调节和系统毛细血管网络动力学之间的相互作用提供了新的见解,揭示了几何和动态因素如何控制红细胞行为和灌注。
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引用次数: 0
Identification of shear stress as a potential vasoconduction signal across microvascular networks 鉴定剪切应力作为微血管网络的潜在血管传导信号。
IF 2.7 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE Pub Date : 2025-07-30 DOI: 10.1016/j.mvr.2025.104855
Nien-Wen Hu , M.M.N. Hossain , Julia Withrow , Ryan Walker , Ali Kazempour , Nikolaos Tsoukias , Donald G. Welsh , Walter L. Murfee , Peter Balogh
The objective of this study was to computationally estimate the effects of vessel specific vasoconstriction on immediate shear stress changes across microvascular networks. Shear stress due to microvascular blood flow is an established initiator of ion-mediated signaling along microvessels which regulates control of microcirculatory blood flow. Yet, beyond initiating local vasomotion in a vessel, shear stress as a vasoconduction signal itself and characteristics of hydrodynamic propagation via blood flow are not well understood. In the current work, we use images of mesenteric microvascular networks from adult rat tissues and a network segmental blood flow model to simulate various vessel constriction scenarios and estimate subsequent shear stress changes and distances these changes spread from the site of constriction. Scenarios involving both arteriolar constriction and capillary constriction are considered, in addition to a microvascular network from muscle tissue. The findings generally reveal heterogenous and physiologically relevant shear stress changes across the networks for all cases, with magnitudes spanning a wide range and can exceed 30 dyne/cm2. Further, physiological relevant wall shear changes were predicted at distances several mm from the stimulus site. Spatial patterns of shear stress change relative to network topology and capillary density are also identified. Altogether, the results invigorate consideration and discussion about shear stress as a potential player in vasoconduction responses.
本研究的目的是通过计算估计血管特异性血管收缩对微血管网络即时剪切应力变化的影响。微血管血流引起的剪切应力是离子介导的微血管信号传导的起始点,它调节微循环血流的控制。然而,除了在血管中启动局部血管舒缩外,剪切应力作为血管传导信号本身以及流体动力学通过血流传播的特征还没有得到很好的理解。在目前的工作中,我们使用成年大鼠组织的肠系膜微血管网络图像和网络段血流模型来模拟各种血管收缩情景,并估计随后的剪切应力变化以及这些变化从收缩部位传播的距离。除了肌肉组织的微血管网络外,还考虑了涉及小动脉收缩和毛细血管收缩的情况。研究结果普遍揭示了所有情况下神经网络的非均质和生理相关的剪切应力变化,其幅度跨越广泛,可超过30达因/平方厘米。此外,在距离刺激部位几毫米的距离上预测了生理相关的壁剪切变化。剪切应力随网络拓扑结构和毛细密度的空间变化规律也得到了识别。总之,这些结果激发了对剪切应力作为血管传导反应的潜在参与者的考虑和讨论。
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引用次数: 0
PCSK9 inhibitor improved cardiac function after acute myocardial infarction in rats PCSK9抑制剂改善大鼠急性心肌梗死后心功能。
IF 2.7 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE Pub Date : 2025-07-24 DOI: 10.1016/j.mvr.2025.104847
Hongjin An , Junju Zhu , Qianqian Li

Background

This study investigated the effects and possible mechanisms of Protein expression of protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab on cardiac function in rats with acute myocardial infarction (AMI).

Methods

The AMI model was established by ligating the left anterior descending coronary artery in rats. The mRNA expression of PCSK9 in myocardial tissues was detected by real-time fluorescent quantitative PCR (RT-qPCR). Echocardiography was used to examine the cardiac function indexes. Hematoxylin-eosin (HE) and Masson stainings were used to detect myocardial pathologic injury. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to detect myocardial infarction area. Serum levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), lactate dehydrogenase (LDH), creatine kinase isoenzymes (CK-MB), cardiac troponin T (cTnT), interleukin-1β (IL-1β), interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were detected by ELISA. CD31 and vascular endothelial growth factor (VEGF) positive expression was detected by immunohistochemistry. Protein expression levels of PCSK9, Bax, Bcl-2, cleaved-caspase3, receptor interacting protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like (MLKL), and p-MLKL were detected in myocardial tissues by western blot.

Results

The mRNA level and protein expression of PCSK9 were significantly increased in AMI rats. PCSK9 inhibitor evolocumab reduced the levels of LDL-C and TC in serum, thereby improving dyslipidemia. And, evolocumab up-regulated the levels of left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and down-regulated the levels of left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic volume (LVESV), and left ventricular end diastolic volume (LVEDV), which in turn improved cardiac function. In addition, evolocumab attenuated myocardial pathological injury, reduced myocardial infarction area, lowered the levels of LDH, CK-MB, cTnT, IL-1β, IL-17, and TNF-α, and inhibited apoptosis rate, down-regulated Bax, cleaved-caspase3, RIPK1, RIPK3, MLKL, p-MLKL expression, and up-regulated Bcl-2 protein expression, CD31 and VEGF positive expression.

Conclusion

The PCSK 9 inhibitor evolocumab improved cardiac function in AMI rats, and the mechanism may be related to the RIPK1/RIPK3/MLKL pathway.
背景:本研究探讨了蛋白转化酶subtilisin/kexin type 9 (PCSK9)抑制剂evolocumab蛋白表达对急性心肌梗死(AMI)大鼠心功能的影响及其可能机制。方法:结扎大鼠左冠状动脉前降支,建立急性心肌梗死模型。采用实时荧光定量PCR (RT-qPCR)检测PCSK9 mRNA在心肌组织中的表达。超声心动图检查心功能指标。苏木精-伊红(HE)染色和Masson染色检测心肌病理损伤。采用2,3,5-三苯四氮唑(TTC)染色检测心肌梗死面积。ELISA法检测血清低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白T (cTnT)、白细胞介素-1β (IL-1β)、白细胞介素-17 (IL-17)、肿瘤坏死因子-α (TNF-α)水平。免疫组化检测CD31和血管内皮生长因子(VEGF)阳性表达。western blot检测心肌组织中PCSK9、Bax、Bcl-2、cleaved-caspase3、受体相互作用蛋白激酶1 (RIPK1)、RIPK3、混合谱系激酶结构域样(MLKL)、p-MLKL的蛋白表达水平。结果:心肌梗死大鼠PCSK9 mRNA水平及蛋白表达显著升高。PCSK9抑制剂evolocumab降低血清LDL-C和TC水平,从而改善血脂异常。evolocumab上调左室射血分数(LVEF)和左室缩短分数(LVFS)水平,下调左室收缩末内径(LVESD)、左室舒张末内径(LVEDD)、左室收缩末容积(LVESV)和左室舒张末容积(LVEDV)水平,进而改善心功能。evolocumab可减轻心肌病理损伤,缩小心肌梗死面积,降低LDH、CK-MB、cTnT、IL-1β、IL-17、TNF-α水平,抑制凋亡率,下调Bax、cleaved-caspase3、RIPK1、RIPK3、MLKL、p-MLKL表达,上调Bcl-2蛋白表达、CD31、VEGF阳性表达。结论:pcsk9抑制剂evolocumab改善AMI大鼠心功能,其机制可能与RIPK1/RIPK3/MLKL通路有关。
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引用次数: 0
Novel in vivo porcine models of chronic ischemic tissue 猪慢性缺血组织的新型体内模型。
IF 2.9 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE Pub Date : 2025-07-19 DOI: 10.1016/j.mvr.2025.104845
Veronika Frelichova , Robert Bem , Jaroslav Chlupac , Michal Dubsky , Jitka Husakova , Andrea Nemcova , Ludek Voska , Zuzana Simunkova , Filip Tichanek , Jiri Fronek
There is a lack of reliable in vivo models that replicate limb-threatening ischemia in humans. To fill this gap, we developed and validated two novel porcine ischemic models: ischemic limb and dorsal flap models, both with and without streptozotocin-induced hyperglycemia (N = 3 per group, 12 in total). Hind limb ischemia model was induced via different arterial ligations, with two ischemic and three control wounds per animal. In the flap model, four full-thickness flaps were created on the dorsum with silicone sheets to block reperfusion, and excisional wounds were made on the top. One non-ischemic wound served as control. Transcutaneous oxygen pressure (TcPO2), wound area, and microvascular density were measured, with TcPO2 and wound area assessed longitudinally. Data analysis focused on detailed visualization and Bayesian hierarchical modelling to account for the small sample size. Developed models exhibited stable ischemia and prolonged wound healing, with TcPO2 remaining under 30 mmHg over 28 days, and wound healing extending beyond two weeks. The flap model showed slower TcPO2 recovery and greater chronicity compared to the limb model, without reliable effect of hyperglycemia. Thus, the porcine flap model shows the highest potential as a relevant model for chronic limb-threatening ischemia.
目前缺乏可靠的体内模型来复制人体肢体缺血。为了填补这一空白,我们开发并验证了两种新的猪缺血模型:缺血肢体和背瓣模型,包括和不包括链脲佐菌素诱导的高血糖(N = 每组3,共12)。采用不同的动脉结扎法建立后肢缺血模型,每只动物2个缺血创口和3个对照创口。在皮瓣模型中,在背侧制作4个全厚皮瓣,用硅胶片阻断再灌注,并在顶部做切除创面。1个非缺血性创面作为对照。测量经皮氧压(TcPO2)、创面面积和微血管密度,纵向评估TcPO2和创面面积。数据分析侧重于详细的可视化和贝叶斯分层建模,以解释小样本量。开发的模型表现出稳定的缺血和延长的伤口愈合,在28 天内TcPO2保持在30 mmHg以下,伤口愈合持续超过两周。与肢体模型相比,皮瓣模型的TcPO2恢复较慢,慢性性更强,无可靠的高血糖效果。因此,猪皮瓣模型作为慢性肢体缺血的相关模型显示出最高的潜力。
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引用次数: 0
Evaluation of neovascularization in murine osteoarthritis using micro-computed tomography 用微计算机断层扫描评价小鼠骨关节炎的新生血管。
IF 2.9 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE Pub Date : 2025-07-16 DOI: 10.1016/j.mvr.2025.104844
Reza Talaie, Pooya Torkian, Anthony Spano, Alexander Clayton, Jafar Golzarian

Purpose

The study aimed to examine neovascularization in murine osteoarthritis (OA) using micro-computed tomography (μCT).

Materials and methods

OA was induced in eighteen mice through intra-articular collagenase injection, designating the left hindlimbs as OA models and the right hindlimbs as controls. Mice were monitored for 4, 8, or 12 weeks post-induction. Hindlimbs underwent overnight tissue fixation and were then subjected to μCT scanning. Quantification of unnamed arterial branches spanned from the femoral artery's terminal branching point to 2.5 mm below the tibial plateau.

Results

Baseline characteristics did not differ significantly between control and OA-induced groups (p > 0.05). Collagenase-treated limbs showed a significantly higher number of unnamed arterial branches compared to controls (11.6 vs. 7.5, p < 0.001), reflecting increased neovascularization. This elevation persisted across all post-induction time points, with no significant time-dependent trend (p = 0.09) or interaction between time and treatment group (p = 0.17). Spatial analysis revealed that neovessels were predominantly localized to peri-meniscal (61 %) and subchondral (29 %) regions.

Conclusion

Collagenase-induced OA in mice results in sustained and spatially patterned neovascularization, detectable using non-contrast μCT. These findings underscore the utility of μCT for tracking vascular remodeling in OA and highlight potential anatomical targets for angiogenesis-modulating therapies.
目的:利用微计算机断层扫描(μCT)观察小鼠骨关节炎(OA)新生血管的形成情况。材料与方法:18只小鼠关节内注射胶原酶诱导OA,左后肢为OA模型,右后肢为对照组。小鼠在诱导后4、8或12 周进行监测。后肢组织固定过夜后进行μCT扫描。从股动脉末端分支点到胫骨平台下2.5 mm的未命名动脉分支的定量。结果:对照组和oa诱导组的基线特征无显著差异(p > 0.05)。与对照组相比,胶原酶治疗的肢体显示出更多的未命名动脉分支(11.6比7.5,p )。结论:通过非对比μCT检测,胶原酶诱导的小鼠OA导致持续和空间模式的新血管形成。这些发现强调了μCT在追踪OA血管重构方面的效用,并强调了血管生成调节疗法的潜在解剖学靶点。
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引用次数: 0
The electrophysiological effects of angiotensin 1–7 on hypertrophic myocardium in spontaneously hypertensive rats 血管紧张素1-7对自发性高血压大鼠肥厚心肌的电生理作用。
IF 2.9 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE Pub Date : 2025-07-13 DOI: 10.1016/j.mvr.2025.104843
Xin Yu , Zhen Yang , Zhilan Ma , Ru Yan , Jianzhong Zhang
This study aimed to explore the effects of Angiotensin 1–7 (Ang1–7) on electrophysiological remodeling of hypertensive hypertrophic myocardium in spontaneously hypertensive rats (SHR). Thirty male SHR rats were equally divided into three groups: SHR control group (SHRC) treated with saline; Ang1–7 group (SHR-A) treated with Ang1–7[25 μg·(kg min)−1] and Ang1–7 blocker group (SHRB) treated with A779 [72 μg·(kg min)−1]. Wistar-Kyoto (WKY) rats (n = 10) were used as a normotensive group. The treatment period was 5 weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Echocardiography was used to evaluate cardiac function. The ventricular myocytes were isolated for evaluation of electrophysiological remodeling of myocardium using microelectrode and patch clamp techniques. When compared with those in WKY rats before treatment, systolic and diastolic pressures were significantly higher in SHR (P < 0.01 and P < 0.001 respectively), left ventricular end-diastolic diameter (LVEDd) was significantly lower (P < 0.05), while diastolic interventricular septum thickness (IVSd), diastolic left ventricular posterior wall thickness (LVPWd) were significantly greater in SHR (P < 0.01). After 5 weeks of treatment, compared with SHR-C group, SBP, DBP, IVSd, LVPWd in SHR-A group were lower significantly (P < 0.05), while SBP in SHR-B group was significantly higher (P < 0.05). Compared with WKY group, the resting potential (RP), action potential amplitude (APA) and transient sodium current (INa-T) in SHR group were significantly lower (P < 0.05), and the action potential duration (APD20, APD50 and APD90) in SHR group was greater (P < 0.05). After Ang1–7 intervention, RP, APA and INa-T were significantly greater in SHR-A than those in SHR-C (P < 0.05), and APD in SHR-A significantly lower than that in SHR-C (P < 0.05). Taken together, these results demonstrated that Ang1–7 can not only decrease the blood pressure, but reverse the myocardial hypertrophy and electrophysiological remodeling as well in SHR rats.
本研究旨在探讨血管紧张素1-7 (Angiotensin 1-7, Ang1-7)对自发性高血压大鼠(SHR)高血压肥厚心肌电生理重构的影响。30只雄性SHR大鼠平均分为3组:SHR对照组(SHRC)生理盐水处理;Ang1-7组(shra)用Ang1-7[25 μg·(kg min)-1]和Ang1-7阻滞剂组(SHRB)用A779[72 μg·(kg min)-1]。Wistar-Kyoto (WKY)大鼠(n = 10)作为正常血压组。治疗时间为5 周。测量收缩压(SBP)和舒张压(DBP)。超声心动图评价心功能。采用微电极和膜片钳技术分离心室肌细胞,评价心肌电生理重构。与治疗前WKY大鼠比较,SHR组收缩压、舒张压均显著升高(P Na-T), SHR组收缩压、舒张压均显著降低(P 20、APD50、APD90), SHR组收缩压、舒张压均显著升高(P Na-T均显著高于SHR- c组(P 20、APD50、APD90)
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引用次数: 0
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Microvascular research
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